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Exosomes derived from LPS-induced MHs cells prompted an inflammatory response in sepsis-induced acute lung injury
Respiratory Physiology & Neurobiology ( IF 2.3 ) Pub Date : 2021-06-06 , DOI: 10.1016/j.resp.2021.103711
Xintong Sui 1 , Wei Liu 1 , Zhi Liu 1
Affiliation  

Exosome is a novel tool with an essential role in cell communication. However, its role in the pathogenesis of sepsis-induced acute lung injury is currently unknown. Here, we first found that lipopolysaccharide (LPS) could up-regulate the expression of pro-inflammatory cytokines and promote exosomes release in the murine alveolar macrophage cell line (MHs cells). Moreover, we found MHs cells derived exosomes also maintain the pro-inflammatory effect after LPS stimulation. Treating with hydrochloride hydrate (GW4869) could dose-dependently downregulated the release of exosomes and inhibited the upregulation of inflammatory cytokines in MHs cells with LPS treatment. Also, we further identified GW4869 administration induced the remission of histopathologic changes, the reduction of pro-inflammatory cytokines in lung tissue, and inhibit serum exosomes release. These results indicate that the downregulation of exosome release by GW4869 might protect lung tissue from LPS induced injury through the suppression of excessive inflammatory responses, suggesting its potential therapeutic effects on sepsis-induced acute lung injury.



中文翻译:

源自 LPS 诱导的 MHs 细胞的外泌体在脓毒症诱导的急性肺损伤中引起炎症反应

外泌体是一种在细胞通讯中具有重要作用的新型工具。然而,目前尚不清楚其在脓毒症引起的急性肺损伤发病机制中的作用。在这里,我们首先发现脂多糖 (LPS) 可以上调促炎细胞因子的表达并促进外泌体在小鼠肺泡巨噬细胞系 (MHs 细胞) 中的释放。此外,我们发现 MHs 细胞衍生的外泌体在 LPS 刺激后也保持促炎作用。用盐酸水合物 (GW4869) 处理可以剂量依赖性地下调外泌体的释放,并抑制 LPS 处理的 MHs 细胞中炎性细胞因子的上调。此外,我们进一步确定 GW4869 给药诱导组织病理学变化的缓解,肺组织中促炎细胞因子的减少,并抑制血清外泌体释放。这些结果表明,GW4869 下调外泌体释放可能通过抑制过度炎症反应来保护肺组织免受 LPS 诱导的损伤,这表明其对脓毒症诱导的急性肺损伤具有潜在的治疗作用。

更新日期:2021-06-08
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